Neuroprotection by T-cells depends on their subtype and activation state

Wolf, Susanne; Fisher, Jasmin; Bechmann, Ingo; Steiner, Barbara; Kwidzinski, Erik; Nitsch, Robert

doi:10.1016/s0165-5728(02)00367-3

Cited by 70 publications

(50 citation statements)

References 52 publications

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“…21 In addition to Treg cells, Th2 cells have been suggested to play a role in neuroprotection but there are discrepancies as to whether this occurs in a contact-dependent or contact-independent manner. 17,[22][23][24] Our findings support the suggestion that T cells can be neuroprotective however further investigation is required to establish the responsible T cell subtypes for these effects under our experimental conditions. Despite the majority of studies focussing on the role of T cells in CNS disorders, recent studies have also proposed a possible role for B cells.…”

supporting

confidence: 82%

“…[13][14][15][16] Our findings are in agreement with a previous study which focused specifically on the consequence of exposing organotypic cultures to the specific T cell subtypes. 17 It revealed that both Th1 and Th2 cells were protective in a contact independent manner and the activation of these cell types led to increased neuroprotection. However in contrast to our study, this protection was against secondary damage initiated by explantation of tissue from living animal to the culture dish whereas our own study utilised established models of neurodegeneration.…”

Section: Discussionmentioning

confidence: 99%

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Lymphocytes Protect Cortical Neurons Against Excitotoxicity Mediated by Kainic Acid, an in vitro Model for Neurodegeneration

Shrestha¹,

Millington

Brewer

et al. 2015

Kathmandu Univ. Med. J.

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BackgroundNeurodegenerative disease is a progressive loss of neurons from the central nervous system (CNS). Various conditions have been implicated for such conditions including ageing, inflammation, stress and genetic predisposition. Recently, studies have linked neurodegeneration with inflammation. Some studies have suggested the harmful effect of immune response while others have argued its neuroprotective role in neurodegeneration of the CNS. However, the precise role of inflammation and immune cells in such condition is still not clear. ObjectiveTo investigate the role of lymphocytes in neurodegeneration of the CNS and determine the underlying mechanism. MethodWe have used 4-7 days old mouse pups (C57Bl6) to prepare organotypic slice cultures which were cultured for 13-15 days prior to experiment. To induced cell death kainic acid was used and considered as an in vitro model for neurodegeneration. Lymphocytes were obtained from peripheral lymph nodes of 5-10 weeks old adult mouse which were used in the current study. Propidium iodide was used as a fluorescent dye to determine cell death in brain slice cultures. ResultLymphocytes do not induce cell death in slice cultures in the absence of any toxic insult whereas, after applying toxic insult to the slice cultures using kainic acid, lymphocytes show neuroprotection against such insult. Similarly, purified nonactivated and purified activated T cells along with T cells depleted lymphocyte preparation also exhibit neuroprotection against kainic acid-induced cell death. We further, have demonstrated that the observed neuroprotection is contactindependent and soluble mediators released from lymphocytes are responsible for the observed neuroprotection. Moreover, our study has revealed that soluble mediators exhibiting neuroprotection act via astrocytes. ConclusionLymphocyte preparations are neuroprotective and the observed neuroprotection is contact-independent. Soluble mediators released from lymphocytes are responsible for the observed neuroprotection. Astrocytes, lymphocytes, neurodegeneration, neuroprotection, t cells Page 133 Original Article KEY WORDS Lymphocyte preparationPeripheral lymph nodes were harvested from C57Bl6 mice (6-10 weeks old) and transferred to complete RPMI 1640 (cRPMI) media containing 10% foetal calf serum and 2mM L-Glutamine. The lymph nodes were triturated and passed through a cell strainer (40µM pore), transferred to a sterile tube and centrifuged at 1400 rpm for five minutes. The pellet was then washed at least two times in culture media and the cells were re-suspended in culture media, counted in the presence of trypan blue to identify viable cells and diluted to 1X10 6 cells per ml, the final concentration used in all experiments. T cells were purified from lymphocyte preparations using magnetic-assorted cell sorting (MACS) and depleting non-T cells using a Pan T Cell Isolation Kit (Miltenyi Biotec, UK) following the manufacturer's instructions. Following T cell isolation, the non-T cell fraction was collected for the ...

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supporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Lymphocytes Protect Cortical Neurons Against Excitotoxicity Mediated by Kainic Acid, an in vitro Model for Neurodegeneration

Shrestha¹,

Millington

Brewer

et al. 2015

Kathmandu Univ. Med. J.

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“…Among the effector T cells that can be locally activated for the benefit of injured tissue are T helper 1 (Th1) and Th2 cells directed to self-antigens (2,38). The characteristic cytokine of these T cells is IFN-␥.…”

Section: Discussionmentioning

confidence: 99%

“…To gain some insight into the mechanisms underlying the beneficial and the inhibitory effects of Treg on neuronal survival, we carried out an in vitro experiment by using OHSCs. With this preparation, excision of the hippocampus corresponds to the primary insult, and the subsequent neural death in vitro is therefore a measure of secondary degeneration of the neural tissue (37,38). Microglia were exposed to activated Teff, Treg, or both, and then Fig.…”

Section: The Treg Neuroprotective Response Is Mediated In Part Throughmentioning

confidence: 99%

Dual effect of CD4⁺CD25⁺regulatory T cells in neurodegeneration: A dialogue with microglia

Kipnis

Avidan

Caspi

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

152

107

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autoimmunity ͉ neuroprotection ͉ neurodegenerative conditions ͉ hippocampal slice cultures ͉ immune regulation T he systemic adaptive T cell-dependent immune response plays a key role in the ability of neurons in the central nervous system (CNS) to withstand injurious conditions (1-3). Studies from our laboratory have shown that, after a CNS injury, T cells nonselectively migrate to the site of injury (4), and suggest that homing T cells, which encounter their relevant antigens at the lesion site, are the ones that contribute to the repair. Such T cells become locally activated to produce neurotrophic factors (5) and cytokines, which are capable of affecting the activity of resident microglia and hence the fate of threatened neurons. We further showed that the T cell-dependent protection evoked after an axonal injury, being an anti-self-response (6), is constitutively limited by naturally occurring CD4 ϩ CD25 ϩ regulatory T cells (Treg) (6). It is, however, amenable to therapeutic boosting, either by postinjury immunization with antigens derived from dominant proteins residing in the site of damage or by depletion of Treg (2).Treg comprise Ϸ10% of the CD4 ϩ T cell population, and have been widely viewed as safeguards against the pathogenic effects of autoimmune CD4 ϩ CD25

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“…Furthermore, it was showed that Th2 cells specific for myelin basic protein had protective effects on neuronal survival. This neuroprotective effect of the antigen-specific T cells was influenced by the extent of non-specific activation of the T cells (Wolf et al, 2002). In another study of peripheral facial nerve injury CD4 + T cells were found to mediate facial motor neurons survival (Serpe et al, 2003).…”

Section: Adaptive Immunitymentioning

confidence: 97%

Traumatic Brain Injury and Inflammation: Emerging Role of Innate and Adaptive Immunity

Dardiotis¹,

Karanikas²,

Paterakis³

et al. 2012

Brain Injury - Pathogenesis, Monitoring, Recovery and Management

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Neuroprotection by T-cells depends on their subtype and activation state

Cited by 70 publications

References 52 publications

Lymphocytes Protect Cortical Neurons Against Excitotoxicity Mediated by Kainic Acid, an in vitro Model for Neurodegeneration

Lymphocytes Protect Cortical Neurons Against Excitotoxicity Mediated by Kainic Acid, an in vitro Model for Neurodegeneration

Dual effect of CD4⁺CD25⁺regulatory T cells in neurodegeneration: A dialogue with microglia

Traumatic Brain Injury and Inflammation: Emerging Role of Innate and Adaptive Immunity

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Neuroprotection by T-cells depends on their subtype and activation state

Cited by 70 publications

References 52 publications

Lymphocytes Protect Cortical Neurons Against Excitotoxicity Mediated by Kainic Acid, an in vitro Model for Neurodegeneration

Lymphocytes Protect Cortical Neurons Against Excitotoxicity Mediated by Kainic Acid, an in vitro Model for Neurodegeneration

Dual effect of CD4+CD25+regulatory T cells in neurodegeneration: A dialogue with microglia

Traumatic Brain Injury and Inflammation: Emerging Role of Innate and Adaptive Immunity

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Dual effect of CD4⁺CD25⁺regulatory T cells in neurodegeneration: A dialogue with microglia